Cancer cells depend on altered nutrient uptake and metabolism to grow and divide. In order to appropriately regulate energy-intensive processes such as growth and proliferation, cells must be able to gauge their metabolic resources. My lab is interested in understanding how cells sense nutrient availability and integrate this information with signaling and transcriptional networks in order to modulate activities such as growth, proliferation, and differentiation. Current research focuses on elucidating the roles of nutrient-sensitive protein modifications in regulating signaling and gene expression in the contexts of cancer and metabolic disease.

We have recently demonstrated that acetylation of histones, and associated changes in gene expression, are responsive to glucose availability in a manner dependent on ATP-citrate lyase (ACL), a metabolic enzyme that cleaves mitochondria-derived citrate to produce acetyl-CoA in the nucleus and cytoplasm. Hence, histones can be modified in a manner responsive to nutrient availability, potentially influencing multiple chromatin-dependent processes. A major current focus of the lab is to elucidate the mechanisms through which ACL regulates acetylation and its impact on signaling and gene expression, using cancer and metabolic cell types and mouse models.

A second area of interest is in understanding the role of the hexosamine biosynthetic pathway in regulating metabolism and growth. The hexosamine pathway is a branch of glucose metabolism that produces UDP-N-acetylglucosamine (UDP-GlcNAc), a donor substrate used in the production of several types of glycans, including N-linked glycans. Many cell surface and secreted proteins are modified co-translationally by N-linked glycosylation, and these glycoproteins can be influenced by metabolic state through glucose flux into the hexosamine pathway. Changes in the function and surface expression of glycoproteins can impact tumor growth by altering cancer cells’ interactions with their environment, including their ability to respond to growth factors and acquire nutrients. We are currently investigating how the hexosamine biosynthetic pathway is regulated in cancer cells and its impact on cancer cell growth and proliferation.

Rotation Projects:

Rotation projects are available in each area of interest in the lab. Please contact Dr. Wellen for details.